Adherence and Quality of Life in Non-Valvular Atrial Fibrillation With Direct Oral Anticoagulants Versus Vitamin K Antagonists: A Systematic Review

Abstract Background Direct anticoagulants (DOACs) and vitamin K antagonists (VKAs) differ in pharmacokinetic characteristics, intensity of required laboratory monitoring, and costs. These differences could affect patients' adherence to treatment and quality of life (QoL). Objective To assess whether patients with non-valvular atrial fibrillation (AF) using DOACs have better treatment adherence and QoL when compared to patients using VKAs. Methods We conducted a systematic review in Medline, Embase, LILACS, SciELO, CINAHL, and Cochrane Central, until June 9, 2021. We included studies that estimated and compared treatment adherence and QoL between DOACs and VKAs in adults with non-valvular AF. The methodological quality of the studies was assessed using the Joanna Briggs Institute (JBI) tools. The protocol was registered in the PROSPERO (CRD 42020165238). Results Sixteen studies, including 122,458 patients with non-valvular AF, evaluated adherence, and eleven studies, including 5,687 patients, assessed QoL. A variety of methods was used to measure adherence. Eleven studies showed no difference in adherence between DOACs and VKAs, while three studies favored VKAs over DOACs and two studies favored DOACs over VKAs. QoL was measured by specific (n = 3) or generic questionnaires (n = 8); results favored DOACs over VKAs in four studies, while in the other seven studies the results showed no difference between the groups. Meta-analyses were not performed due to high methodological heterogeneity among studies. Conclusions Available evidence regarding treatment adherence and QoL with DOACs and VKAs is characterized by methodological heterogeneity and conflicting findings.

The Use of the Target Trial Approach in Perinatal Pharmacoepidemiology: A Scoping Review Protocol.

Background: Pregnant and postpartum women have been historically excluded from clinical trials, with data on the safety of drugs relying on observational research. Methodological concerns regarding the timing and dosing of medications, data sources, study designs, and methods used for estimating associations are still problematic in observational studies. Answering causal questions is even more complex. Despite the increased interest in emulating target trials using observational data, little is known about this approach in perinatal pharmacoepidemiology. Objective: This scoping review protocol aims to describe the methodology for assessing the available literature concerning emulating target trials for studying outcomes in women exposed to medications in the preconception, perinatal, or postpartum periods. Methods and Analysis: We will follow the methods detailed in the Joanna Briggs Institute reviewer's manual. We will adopt the six-stage framework recommended by Arksey and O'Malley and Levac and others. Web scraping techniques will be used for identifying relevant studies. Two authors will select articles based on the title and abstract, with discrepancies resolved by consensus, by a third reviewer. Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews flow diagram will be presented to reflect the search process. We will use existing statements to identify quality gaps in the current literature. Variables related to the content for perinatal pharmacoepidemiologic research will be included. The Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I) will guide the assessment of the target trial emulation (i.e., treatment strategies compared, assignment procedures, follow-up period, outcome, and causal contrasts). Discussion: Data regarding the safety of drugs taken, prior to and during pregnancy and while lactating are lacking and it is necessary to understand how we can answer these questions using rigorous methods in observational research. Through this scoping review, we intend to understand to what extent the target trial approach is being used in perinatal pharmacoepidemiology and provide recommendations to improve its use in this field. Ethics and Dissemination: Secondary data from published scientific articles will be used, not requiring approval by the Research Ethics Committee with human beings. Findings will be submitted to a peer-reviewed journal.

Prevalence of chronic respiratory diseases and medication use among children and adolescents in Brazil - a population based cross-sectional study / Prevalência de doenças respiratórias crônicas e uso de medicamentos entre crianças e adolescentes no Brasil - um estudo transversal de base populacional

Abstract Objectives: to describe the prevalence of chronic respiratory diseases and their pharmacological management in children and adolescents in Brazil. Methods: data from the Pesquisa Nacional de Acesso, Uso e Promoção do Uso Racional de Medicamentos no Brasil (PNAUM)(National Access Survey, Use and Promotion of Rational Use of Medicines in Brazil),a population-based cross-sectional study, were analyzed. Household surveys were conducted between September 2013 and February 2014. We included the population under 20 years of age with chronic respiratory diseases. Prevalence of disease, indication of pharmacological treatment, and their use were assessed. Results: the prevalence of chronic respiratory diseases in children aged less than 6 years old was 6.1% (CI95%= 5.0-7.4), 4.7% (CI95%= 3.4-6.4) in those 6-12 years, and 3.9% (CI95%= 2.8-5.4) in children 13 years and older. Children under 6 showed a higher prevalence of pharmacological treatment indication (74.6%; CI95%= 66.0-81.7), as well as medication use (72.6%; CI95%= 62.8-80.7). Of those using inhalers, 56.6% reported using it with a spacer. The most frequent pharmacologic classes reported were short-acting β2 agonists (19.0%), followed by antihistamines (17.2%). Conclusion: children and adolescents who report chronic respiratory diseases living in urban areas in Brazil seem to be undertreated for their chronic conditions. Pharmacological treatment, even if indicated, was not used, an important finding for decision-making in this population.

Resumo Objetivos: descrever a prevalência de doenças respiratórias crônicas e seu manejo farmacológico em crianças e adolescentes no Brasil. Métodos: foram analisados os dados da Pesquisa Nacional de Acesso, Uso e Promoção do Uso Racional de Medicamentos no Brasil (PNAUM), um estudo transversal de base populacional. As pesquisas domiciliares foram realizadas entre setembro de 2013 e fevereiro de 2014. Incluímos a população com menos de 20 anos de idade com doenças respiratórias crônicas. Foi avaliada a prevalência de doença, indicação de tratamento farmacológico e seu uso. Resultados: a prevalência de doenças respiratórias crônicas em menores de 6 anos foi de 6,1% (IC95%= 5,0-7,4), 4,7% (IC95%= 3,4-6,4) naqueles 6-12 anos e 3,9% (IC95%= 2,8-5,4) em crianças com 13 anos ou mais. Crianças menores de 6 anos apresentaram uma maior prevalência de indicação de tratamento farmacológico (74,6%; IC95%= 66,0-81,7), assim como uso de medicamentos (72,6%; IC95%= 62,8-80,7). Dos usuários de inaladores, 56,6% relataram o uso com espaçador. As classes farmacológicas mais frequentemente relatadas foram β2 agonistas de curta ação (19,0%), seguidos por anti-histamínicos (17,2%). Conclusão: crianças e adolescentes que relatam doenças respiratórias crônicas residentes em áreas urbanas no Brasil parecem ser subtratados para suas condições crônicas. O tratamento farmacológico, mesmo quando indicado, não foi utilizado em sua totalidade, um achado importante para a tomada de decisão nessa população.

Maternal Mortality in Brazil, 1990 to 2019: a systematic analysis of the Global Burden of Disease Study 2019.

INTRODUCTION: Maternal death continues to be one of the most challenging public health problems that needs to be addressed in low and middle-income countries. The objective of this study was to describe the problem of maternal death in Brazil, using estimates from the Global Burden of Disease Study (GBD). METHODS: This study used data from the GBD 2019 to show the numbers of deaths and the Maternal Mortality Ratio (MMR) - number of deaths/100,000 live births - in Brazil and its 27 Federated Units (FU), for ages 10 to 54 years, from 1990 to 2019. The annual variation of the MMR was estimated in 1990, 2010, and 2019. The MMR were shown for specific causes as well as for five-year age groups. The estimates were presented with 95% uncertainty intervals (UI). RESULTS: The number of maternal deaths, as well as the MMR showed a 49% reduction from 1990 to 2019. This reduction occurred heterogeneously throughout the country, and the profile of the MMR for specific causes changed between 1990 and 2019: from hypertensive gestation diseases, to indirect maternal deaths, followed by hypertensive gestation diseases. In the extreme age groups, the MMR is higher, with mortality increasing exponentially in direct proportion with age. CONCLUSIONS: Maternal deaths in Brazil have decreased substantially since 1990; however, the numbers still fall short of what was established by the World Health Organization (WHO). Indirect causes are the greatest problem in more than 60% of the FU, especially for hypertensive pregnancy diseases.

Data sources for drug utilization research in Latin American countries-A cross-national study: DASDUR-LATAM study.

PURPOSE: Drug utilization research (DUR) contributes to inform policymaking and to strengthen health systems. The availability of data sources is the first step for conducting DUR. However, documents that systematize these data sources in Latin American (LatAm) countries are not known. We compiled the potential data sources for DUR in the LatAm region. METHODS: A network of DUR experts from nine LatAm countries was assembled and experts conducted: (i) a website search of the government, academic, and private health institutions; (ii) screening of eligible data sources, and (iii) liaising with national experts in pharmacoepidemiology (via an online survey). The data sources were characterized by accessibility, geographic granularity, setting, sector of the data, sources and type of the data. Descriptive analyses were performed. RESULTS: We identified 125 data sources for DUR in nine LatAm countries. Thirty-eight (30%) of them were publicly and conveniently available; 89 (71%) were accessible with limitations, and 18 (14%) were not accessible or lacked clear rules for data access. From the 125 data sources, 76 (61%) were from the public sector only; 46 (37%) were from pharmacy records; 43 (34%) came from ambulatory settings and; 85 (68%) gave access to individual patient-level data. CONCLUSIONS: Although multiple sources for DUR are available in LatAm countries, the accessibility is a major challenge. The procedures for accessing DUR data should be transparent, feasible, affordable, and protocol-driven. This inventory could permit a comparison of drug utilization between countries identifying potential medication-related problems that need further exploration.

Maternal Mortality in Brazil, 1990 to 2019: a systematic analysis of the Global Burden of Disease Study 2019

Abstract INTRODUCTION Maternal death continues to be one of the most challenging public health problems that needs to be addressed in low and middle-income countries. The objective of this study was to describe the problem of maternal death in Brazil, using estimates from the Global Burden of Disease Study (GBD). METHODS This study used data from the GBD 2019 to show the numbers of deaths and the Maternal Mortality Ratio (MMR) - number of deaths/100,000 live births - in Brazil and its 27 Federated Units (FU), for ages 10 to 54 years, from 1990 to 2019. The annual variation of the MMR was estimated in 1990, 2010, and 2019. The MMR were shown for specific causes as well as for five-year age groups. The estimates were presented with 95% uncertainty intervals (UI). RESULTS The number of maternal deaths, as well as the MMR showed a 49% reduction from 1990 to 2019. This reduction occurred heterogeneously throughout the country, and the profile of the MMR for specific causes changed between 1990 and 2019: from hypertensive gestation diseases, to indirect maternal deaths, followed by hypertensive gestation diseases. In the extreme age groups, the MMR is higher, with mortality increasing exponentially in direct proportion with age. CONCLUSIONS Maternal deaths in Brazil have decreased substantially since 1990; however, the numbers still fall short of what was established by the World Health Organization (WHO). Indirect causes are the greatest problem in more than 60% of the FU, especially for hypertensive pregnancy diseases.

Data transparency for building a stronger healthcare system: A case study from Argentinean administrative drug utilization data sources.

In order to compile an inventory of national data sources for drug utilization research (DUR) in Argentina and to verify publicly available data sources, we performed a cross-sectional study that sought to identify national and provincial databases of drug use. In July 2020, we searched the websites of government institutions, carried out a systematic query of bibliographic databases for "drug utilization research" conducted in Argentina, and conducted a survey with local experts. Data collected included: the institution responsible for the database, population covered, accessibility, source of the data, healthcare setting, geographic information, and whether data were individual or aggregated. Descriptive analyses were then performed. We identified 31 data sources for DUR; only one was publicly and conveniently accessible. Five published aggregated data and provide more detailed access by formal request. Only seven sources (23%) reported national data, and most (n=29) included only data from the public healthcare sector. Although data sources for DUR have been found in Argentina, limited access by researchers and policymakers is still an significant obstacle. Increasing health data transparency by making data sources publicly available for the purpose of analyzing public health information is crucial for building a stronger health system.

Para realizar un inventario de fuentes de datos nacionales sobre utilización de medicamentos en Argentina y verificar las fuentes de datos disponibles públicamente, llevamos a cabo un estudio transversal que investiga la existencia de bases de datos nacionales y provinciales sobre utilización de medicamentos. En julio de 2020, realizamos una búsqueda en sitios web de instituciones gubernamentales, una búsqueda sistemática en bases de datos bibliográficas sobre "drug utilization research" en Argentina y una encuesta de expertos. Se identificaron 31 fuentes de datos de utilización de medicamentos, solo una era de acceso público y conveniente, cinco publicaban datos agregados y proporcionaban un acceso más detallado mediante solicitud formal, solo siete fuentes (23%) informaban datos nacionales, y la mayoría de ellas (n=29) incluían solo datos del sector público de salud. Aunque se han encontrado fuentes de datos de utilización de medicamentos en Argentina, el acceso a investigadores y legisladores sigue siendo una barrera importante. Aumentar la transparencia de los datos de salud a través de fuentes disponibles públicamente para analizar la información de salud pública es crucial para construir un sistema de salud más sólido.

Data Sources for Drug Utilization Research in Brazil-DUR-BRA Study.

Background: In Brazil, studies that map electronic healthcare databases in order to assess their suitability for use in pharmacoepidemiologic research are lacking. We aimed to identify, catalogue, and characterize Brazilian data sources for Drug Utilization Research (DUR). Methods: The present study is part of the project entitled, "Publicly Available Data Sources for Drug Utilization Research in Latin American (LatAm) Countries." A network of Brazilian health experts was assembled to map secondary administrative data from healthcare organizations that might provide information related to medication use. A multi-phase approach including internet search of institutional government websites, traditional bibliographic databases, and experts' input was used for mapping the data sources. The reviewers searched, screened and selected the data sources independently; disagreements were resolved by consensus. Data sources were grouped into the following categories: 1) automated databases; 2) Electronic Medical Records (EMR); 3) national surveys or datasets; 4) adverse event reporting systems; and 5) others. Each data source was characterized by accessibility, geographic granularity, setting, type of data (aggregate or individual-level), and years of coverage. We also searched for publications related to each data source. Results: A total of 62 data sources were identified and screened; 38 met the eligibility criteria for inclusion and were fully characterized. We grouped 23 (60%) as automated databases, four (11%) as adverse event reporting systems, four (11%) as EMRs, three (8%) as national surveys or datasets, and four (11%) as other types. Eighteen (47%) were classified as publicly and conveniently accessible online; providing information at national level. Most of them offered more than 5 years of comprehensive data coverage, and presented data at both the individual and aggregated levels. No information about population coverage was found. Drug coding is not uniform; each data source has its own coding system, depending on the purpose of the data. At least one scientific publication was found for each publicly available data source. Conclusions: There are several types of data sources for DUR in Brazil, but a uniform system for drug classification and data quality evaluation does not exist. The extent of population covered by year is unknown. Our comprehensive and structured inventory reveals a need for full characterization of these data sources.

Transparencia de datos para construir un sistema de salud más sólido: estudio de caso de bases de datos administrativas argentinas sobre utilización de medicamentos / Data transparency for building a stronger healthcare system: A case study from Argentinean administrative drug utilization data sources

RESUMEN Para realizar un inventario de fuentes de datos nacionales sobre utilización de medicamentos en Argentina y verificar las fuentes de datos disponibles públicamente, llevamos a cabo un estudio transversal que investiga la existencia de bases de datos nacionales y provinciales sobre utilización de medicamentos. En julio de 2020, realizamos una búsqueda en sitios web de instituciones gubernamentales, una búsqueda sistemática en bases de datos bibliográficas sobre "drug utilization research" en Argentina y una encuesta de expertos. Se identificaron 31 fuentes de datos de utilización de medicamentos, solo una era de acceso público y conveniente, cinco publicaban datos agregados y proporcionaban un acceso más detallado mediante solicitud formal, solo siete fuentes (23%) informaban datos nacionales, y la mayoría de ellas (n=29) incluían solo datos del sector público de salud. Aunque se han encontrado fuentes de datos de utilización de medicamentos en Argentina, el acceso a investigadores y legisladores sigue siendo una barrera importante. Aumentar la transparencia de los datos de salud a través de fuentes disponibles públicamente para analizar la información de salud pública es crucial para construir un sistema de salud más sólido.

ABSTRACT In order to compile an inventory of national data sources for drug utilization research (DUR) in Argentina and to verify publicly available data sources, we performed a cross-sectional study that sought to identify national and provincial databases of drug use. In July 2020, we searched the websites of government institutions, carried out a systematic query of bibliographic databases for "drug utilization research" conducted in Argentina, and conducted a survey with local experts. Data collected included: the institution responsible for the database, population covered, accessibility, source of the data, healthcare setting, geographic information, and whether data were individual or aggregated. Descriptive analyses were then performed. We identified 31 data sources for DUR; only one was publicly and conveniently accessible. Five published aggregated data and provide more detailed access by formal request. Only seven sources (23%) reported national data, and most (n=29) included only data from the public healthcare sector. Although data sources for DUR have been found in Argentina, limited access by researchers and policymakers is still an significant obstacle. Increasing health data transparency by making data sources publicly available for the purpose of analyzing public health information is crucial for building a stronger health system.

Hypertensive Disorders of Pregnancy and Medication Use in the 2015 Pelotas (Brazil) Birth Cohort Study.

Hypertensive disorders of pregnancy account for approximately 22% of all maternal deaths in Latin America and the Caribbean. Pharmacotherapies play an important role in preventing and reducing the occurrence of adverse outcomes. However, the patterns of medications used for treating women with hypertensive disorders of pregnancy (HDP) living in this country is unclear. A population-based birth cohort study including 4262 women was conducted to describe the pattern of use of cardiovascular agents and acetylsalicylic acid between women with and without HDP in the 2015 Pelotas (Brazil) Birth Cohort. The prevalence of maternal and perinatal outcomes in this population was also assessed. HDP were classified according to Ministry of Health recommendations. Medications were defined using the Anatomical Therapeutic Chemical Classification System and the substance name. In this cohort, 1336 (31.3%) of women had HDP. Gestational hypertension was present in 636 (47.6%) women, 409 (30.6%) had chronic hypertension, 191 (14.3%) pre-eclampsia, and 89 (6.7%) pre-eclampsia superimposed on chronic hypertension. Approximately 70% of women with HDP reported not using any cardiovascular medications. Methyldopa in monotherapy was the most frequent treatment (16%), regardless of the type of HDP. Omega-3 was the medication most frequently reported by women without HDP. Preterm delivery, caesarean section, low birth weight, and neonatal intensive care admissions were more prevalent in women with HDP. Patterns of use of methyldopa were in-line with the Brazilian guidelines as the first-line therapy for HDP. However, the large number of women with HDP not using medications to manage HDP requires further investigation.

Epidemiology and burden of chronic respiratory diseases in Brazil from 1990 to 2017: analysis for the Global Burden of Disease 2017 Study.

INTRODUCTION: In Brazil, little is known about the trends of chronic respiratory diseases, which was estimated as the third leading cause of deaths in 2017 worldwide. METHODS: We analyzed Global Burden of Disease (GBD) 2017 estimates for prevalence, incidence, mortality, disability-adjusted life years (DALY), a summary measure of years of life lost (YLLs) and years lived with disability (YLDs), and risk factors attributable to chronic respiratory diseases in Brazil from 1990 to 2017. RESULTS: The overall estimates have decreased for all ages and both sexes, and for age-standardized rates. For age-adjusted prevalence, there was a 21% reduction, and nearly 16% reduction for incidence. There was a 42% reduction in mortality for both sexes, though the rate of deaths for men was 30% greater than the rate in women. The increase in the number of DALY was essentially due to the population growth and population ageing. We observed a 34% increase in the absolute number of DALY in Brazil over the study period. The majority of the DALY rates were due to Chronic Obstructive Pulmonary Disease (COPD). For all ages and both sexes, smoking was the main attributable risk factor. CONCLUSION: In Brazil, although mortality, prevalence and incidence for chronic respiratory diseases have decreased over the years, attention should be taken to the DALYs increase. Smoking remained as the main risk factor, despite the significant decrease of tobacco use, reinforcing the need for maintenance of policies and programs directed at its cessation.

Scientific production on Covid-19 in Brazil: a scoping review / Produção científica sobre a Covid-19 no Brasil: uma revisão de escopo

Introduction: the national scientific production on Covid-19 has an immediate role in developing policies to tackle the disease and for guiding clinical decisions. Objective: to identify and characterize the scientific production on topics related to Covid-19 in national journals from articles published between December 1, 2019, and May 2, 2020. Method: scoping review, whose search for articles occurred in the SciELO Collection Brazil and on the websites of journal Visa em Debate and Ciência & Saúde Coletiva. The validated database was assessed by a simple quantitative analysis to provide numerical summaries of the characteristics of interest in the literature included in the review. Results: 58 (20.8%) articles from 22 national journals were included. The largest number of articles came from journals that developed fast publishing options or had been adopting a continuous flow publication model (n = 45; 77.6%). The distribution of articles in seven research categories was, in this order: Comment (n = 43; 74.1%), Descriptive study (n = 8; 13.8%), Literature review (n = 6; 10.4 %) and Analytical study (n = 1; 1.7%). Only one systematic review was found and the analytical study was classified as an ecological study. April concentrated 86.2% of the articles published, with the peak of publications occurring on April 9 (8 articles). Among 58 articles, "Social isolation, mental health and other aspects related to social behaviours" was the most prevalent theme (n = 14; 24.1%). Conclusions: this scoping review produced a map of scientific production in Brazil on Covid-19. There are important gaps, especially concerning randomized clinical trials and cohort studies, which need to be filled on further research in our country.

Introdução: a produção científica nacional sobre a Covid-19 tem papel imediato na formulação de políticas de enfrentamento da doença e na orientação de decisões clínicas. Objetivo: identificar e caracterizar a produção científica sobre assuntos relacionados à Covid-19 em revistas nacionais a partir de artigos publicados entre 1º de dezembro de 2019 e 2 de maio de 2020. Método: revisão de escopo, cuja busca por artigos ocorreu na Coleção SciELO Brasil e nos sítios eletrônicos das revistas Visa em Debate e Ciência & Saúde Coletiva. O banco de dados validado foi submetido a uma análise quantitativa simples para fornecer resumos numéricos das características de interesse da literatura incluída na revisão. Resultados: foram incluídos 58 (20,8%) artigos provenientes de 22 revistas nacionais. O maior número de artigos proveio das revistas que desenvolveram opções rápidas de publicação ou vinham adotando um modelo de publicação de fluxo contínuo (n = 45; 77,6%). A distribuição dos artigos em sete categorias de pesquisa foi, nesta ordem: Comentário (n = 43; 74,1%), Estudo descritivo (n = 8; 13,8%), Revisão da literatura (n = 6; 10,4%) e Estudo analítico (n = 1; 1,7%). Constatou-se apenas uma revisão sistemática e o estudo analítico publicado foi do tipo ecológico. O mês de abril concentrou 86,2% dos artigos, cujo maior pico, compreendendo o período estudado, ocorreu em 9 de abril, com 8 publicações. Dos 58 artigos, o "Isolamento social, saúde mental e outros aspectos relacionados a comportamentos sociais" foi o tema mais prevalente (n = 14; 24,1%). Conclusões: Esta revisão de escopo produziu um mapa da produção científica no Brasil sobre a Covida-19. Nesta produção, há lacunas importantes, principalmente, no que tange aos ensaios clínicos randomizados e estudos de coorte, que precisam ser preenchidas com a realização de pesquisas.

Protocol implementation for venous thromboembolism prophylaxis: a before-and-after study in medical and surgical patients. / Implementação de protocolo para profilaxia de tromboembolismo venoso: um estudo antes e depois em pacientes clínicos e cirúrgicos.

OBJECTIVE: This study aimed to assess the adequacy of venous thromboembolism (VTE) prophylaxis prescription after a protocol implementation. METHODS: This was a before-and-after study conducted in a tertiary care hospital in Rio Grande do Sul, Southern Brazil. Medical and surgical inpatients aged 18 years or older were assessed for VTE risk and subsequently for thromboprophylaxis adequacy, according to their risk. The evaluations occurred before and after the protocol strategy implementation; it consisted of an online platform to access the protocol, a public posting of the protocol diagram, clinical alerts on the medical staff TV, e-mail alerts, and pop-up alerts on the computerized physician order entry system. The main outcome measure was the adequacy of VTE prophylaxis prescription according to the protocol. RESULTS: A total of 429 patients were evaluated for thromboprophylaxis adequacy (213 before and 216 after). The prevalence of adequacy increased from 54% to 63% (pre and post-intervention, respectively), and after adjustment for patient type and phase of the study, the prevalence ratio reached (PR)=1.20, 95% confidence interval (CI) 1.02-1.42. CONCLUSION: The results showed that the overall appropriateness of thromboprophylaxis prescription was weakly improved. Despite these results, this study provides evidence to date a bunch of strategies for protocol implementations in private institutions in middle-income countries with an open medical staff, as there are few studies investigating these simple and pragmatic interventions.

OBJETIVO: Este estudo visou avaliar a adequação da prescrição de profilaxia de tromboembolismo venoso (TEV) após a implementação do protocolo. MÉTODOS: Trata-se de um estudo antes e depois realizado em um hospital de cuidados terciários no Rio Grande do Sul, Brasil. Pacientes clínicos e cirúrgicos internados, com 18 anos ou mais, foram avaliados para o risco de TEV e, posteriormente, para adequação da tromboprofilaxia, de acordo com o risco. As avaliações ocorreram antes e depois de uma estratégia de implementação de protocolo, que consistiu em uma plataforma on-line para acessar o protocolo, uma postagem pública do diagrama do protocolo, alertas clínicos na sala de convívio médico, alertas de e-mail e alertas pop-up no sistema informatizado de prescrição médica. O Desfecho principal foi a adequação da prescrição de profilaxia do TEV de acordo com o protocolo. RESULTADOS: Foram avaliados 429 pacientes para adequação da tromboprofilaxia (213 antes e 216 depois). A prevalência de adequação aumentou de 54% para 63% (pré e pós-intervenção, respectivamente) e após o ajuste por tipo de paciente e fase do estudo, a razão de prevalência atingiu (RP) = 1,20, intervalo de confiança de 95% (IC) 1,02-1,42. CONCLUSÕES: os resultados mostraram que a adequação geral da prescrição de tromboprofilaxia foi discretamente melhorada. Apesar desses resultados, este estudo fornece evidências, até o momento, de uma série de estratégias para implementar o protocolo em instituições privadas em países de renda média com uma equipe médica aberta, pois há poucas pesquisas investigando esse tipo de intervenção simples e pragmática.

Implementação de protocolo para profilaxia de tromboembolismo venoso: um estudo antes e depois em pacientes clínicos e cirúrgicos / Protocol implementation for venous thromboembolism prophylaxis: a before-and-after study in medical and surgical patients

RESUMO Objetivo Este estudo visou avaliar a adequação da prescrição de profilaxia de tromboembolismo venoso (TEV) após a implementação do protocolo. Métodos Trata-se de um estudo antes e depois realizado em um hospital de cuidados terciários no Rio Grande do Sul, Brasil. Pacientes clínicos e cirúrgicos internados, com 18 anos ou mais, foram avaliados para o risco de TEV e, posteriormente, para adequação da tromboprofilaxia, de acordo com o risco. As avaliações ocorreram antes e depois de uma estratégia de implementação de protocolo, que consistiu em uma plataforma on-line para acessar o protocolo, uma postagem pública do diagrama do protocolo, alertas clínicos na sala de convívio médico, alertas de e-mail e alertas pop-up no sistema informatizado de prescrição médica. O Desfecho principal foi a adequação da prescrição de profilaxia do TEV de acordo com o protocolo. Resultados Foram avaliados 429 pacientes para adequação da tromboprofilaxia (213 antes e 216 depois). A prevalência de adequação aumentou de 54% para 63% (pré e pós-intervenção, respectivamente) e após o ajuste por tipo de paciente e fase do estudo, a razão de prevalência atingiu (RP) = 1,20, intervalo de confiança de 95% (IC) 1,02-1,42. Conclusões os resultados mostraram que a adequação geral da prescrição de tromboprofilaxia foi discretamente melhorada. Apesar desses resultados, este estudo fornece evidências, até o momento, de uma série de estratégias para implementar o protocolo em instituições privadas em países de renda média com uma equipe médica aberta, pois há poucas pesquisas investigando esse tipo de intervenção simples e pragmática.

ABSTRACT Objective This study aimed to assess the adequacy of venous thromboembolism (VTE) prophylaxis prescription after a protocol implementation. Methods This was a before-and-after study conducted in a tertiary care hospital in Rio Grande do Sul, Southern Brazil. Medical and surgical inpatients aged 18 years or older were assessed for VTE risk and subsequently for thromboprophylaxis adequacy, according to their risk. The evaluations occurred before and after the protocol strategy implementation; it consisted of an online platform to access the protocol, a public posting of the protocol diagram, clinical alerts on the medical staff TV, e-mail alerts, and pop-up alerts on the computerized physician order entry system. The main outcome measure was the adequacy of VTE prophylaxis prescription according to the protocol. Results A total of 429 patients were evaluated for thromboprophylaxis adequacy (213 before and 216 after). The prevalence of adequacy increased from 54% to 63% (pre and post-intervention, respectively), and after adjustment for patient type and phase of the study, the prevalence ratio reached (PR)=1.20, 95% confidence interval (CI) 1.02-1.42. Conclusion The results showed that the overall appropriateness of thromboprophylaxis prescription was weakly improved. Despite these results, this study provides evidence to date a bunch of strategies for protocol implementations in private institutions in middle-income countries with an open medical staff, as there are few studies investigating these simple and pragmatic interventions.

Epidemiology and burden of chronic respiratory diseases in Brazil from 1990 to 2017: analysis for the Global Burden of Disease 2017 Study / Epidemiologia e carga das doenças respiratórias crônicas no Brasil de 1990 a 2017: análise do Estudo Global Burden of Disease 2017

ABSTRACT: Introduction: In Brazil, little is known about the trends of chronic respiratory diseases, which was estimated as the third leading cause of deaths in 2017 worldwide. Methods: We analyzed Global Burden of Disease (GBD) 2017 estimates for prevalence, incidence, mortality, disability-adjusted life years (DALY), a summary measure of years of life lost (YLLs) and years lived with disability (YLDs), and risk factors attributable to chronic respiratory diseases in Brazil from 1990 to 2017. Results: The overall estimates have decreased for all ages and both sexes, and for age-standardized rates. For age-adjusted prevalence, there was a 21% reduction, and nearly 16% reduction for incidence. There was a 42% reduction in mortality for both sexes, though the rate of deaths for men was 30% greater than the rate in women. The increase in the number of DALY was essentially due to the population growth and population ageing. We observed a 34% increase in the absolute number of DALY in Brazil over the study period. The majority of the DALY rates were due to Chronic Obstructive Pulmonary Disease (COPD). For all ages and both sexes, smoking was the main attributable risk factor. Conclusion: In Brazil, although mortality, prevalence and incidence for chronic respiratory diseases have decreased over the years, attention should be taken to the DALYs increase. Smoking remained as the main risk factor, despite the significant decrease of tobacco use, reinforcing the need for maintenance of policies and programs directed at its cessation.

RESUMO: Introdução: No Brasil, pouco se sabe sobre as tendências das doenças respiratórias crônicas, que foram estimadas como a terceira principal causa de mortes em 2017 em todo o mundo. Métodos: Analisamos as estimativas do Global Burden of Disease (GBD) 2017 para prevalência, incidência, mortalidade, anos de vida ajustados por incapacidade (DALY), uma medida resumida de anos de vida perdidos (YLL) e anos vividos com deficiência (YLD), e fatores de risco atribuíveis a doenças respiratórias crônicas no Brasil, de 1990 a 2017. Resultados: As estimativas gerais diminuíram para todas as idades e ambos os sexos, assim como para as taxas padronizadas por idade. Para a prevalência ajustada pela idade, houve uma redução de 21% e, aproximadamente, 16% para a incidência. Houve uma redução de 42% na mortalidade para ambos os sexos, embora a taxa de mortes para homens tenha sido 30% maior do que a taxa para mulheres. O aumento no número de DALY deveu-se ao crescimento e envelhecimento da população. Observamos um aumento de 34% no número absoluto de DALYs no Brasil durante o período do estudo. A maioria das taxas de DALY foi devido a Doença Pulmonar Obstrutiva Crônica (DPOC). Para todas as idades e ambos os sexos, tabagismo foi o principal fator de risco atribuível. Conclusão: No Brasil, embora a mortalidade, a prevalência e a incidência de doenças respiratórias crônicas tenham diminuído ao longo dos anos, maior atenção deve ser dada ao aumento dos DALYs. O tabagismo permaneceu como principal fator de risco, apesar da redução significativa do seu uso, reforçando a necessidade de manutenção de políticas e programas direcionados à sua cessação.

[Indication, access, and use of medicines for chronic respiratory diseases in Brazil: results from the National Survey on Access, Utilization, and Promotion of Rational Use of Medicines in Brazil (PNAUM), 2014]. / Indicação, acesso e utilização de medicamentos para doenças respiratórias crônicas no Brasil: resultados da Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos no Brasil (PNAUM), 2014.

The study aimed to estimate the prevalence of self-reported chronic respiratory diseases and the indication, access to, and use of medicines, as well as their sources, in the Brazilian adult population. Data were analyzed on adults 20 years and older from the National Survey on Access, Utilization, and Promotion of Rational Use of Medicines in Brazil (PNAUM), conducted from September 2013 to February 2014. Prevalence of chronic respiratory diseases was 3% (95%CI: 2.7-3.3). Of these individuals, 58.1% (95%CI: 51.8-64.0) had an indication for pharmacological treatment. Of those with indication for treatment, 77.1% (95%CI: 71.0-82.8) were using at least one of the prescribed drugs. Total access to therapy was 91.4% (95%CI: 79.9-96.6), and more than half of individuals with chronic respiratory diseases purchased at least one of the drugs in retail pharmacies (57.3%). The most frequently reported drug class was the association of a corticosteroid plus a long-acting beta-2 agonist in inhalation form, the most common example of which was the association budesonide/formoterol (20.3%; 95%CI: 16.0-25.4). According to our study, prevalence of self-reported chronic respiratory diseases was lower than in previous studies published on the Brazilian population. Nearly half of the population reporting chronic respiratory diseases did not have an indication for pharmacological treatment. Among those with such indication, approximately one-fourth were not using medications during the study period, and for those who were on medication, although access was high, they had to pay for their medicines.

O objetivo foi estimar a prevalência de doenças respiratórias crônicas autorreferidas, a indicação, o acesso e o uso de medicamentos, bem como fontes de obtenção, na população adulta brasileira. Foram analisados dados de adultos com idade maior ou igual a 20 anos, provenientes da Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos no Brasil (PNAUM), realizada entre setembro de 2013 e fevereiro de 2014. A prevalência de doenças respiratórias crônicas foi de 3% (IC95%: 2,7-3,3). Desses, 58,1% (IC95%: 51,8-64,0) tinham indicação de tratamento farmacológico. Daqueles com indicação de tratamento, 77,1% (IC95%: 71,0-82,8) estavam utilizando pelo menos um dos medicamentos indicados. O acesso total à terapia foi de 91,4% (IC95%: 79,9-96,6), sendo que mais da metade das pessoas com doenças respiratórias crônicas adquiria pelo menos um de seus medicamentos em farmácias comerciais (57,3%). A classe de medicamentos mais referida foi a associação beta-2 agonista de longa duração e corticosteroides sob a forma inalatória, cujo representante mais frequente foi a associação budesonida/formoterol (20,3%; IC95%: 16,0-25,4). De acordo com o nosso estudo, a prevalência de doenças respiratórias crônicas autorreferida foi inferior a trabalhos previamente publicados para a população brasileira. Verificou-se que quase metade da população que referiu doenças respiratórias crônicas não tinha indicação de tratamento farmacológico. Já aqueles com indicação, aproximadamente um quarto não utilizava os medicamentos no período do estudo e, para os que usavam, embora o acesso fosse elevado, precisavam pagar para adquirir seus tratamentos.

El objetivo fue estimar la prevalencia de enfermedades respiratorias crónicas autoinformadas, la indicación, el acceso y el uso de medicamentos, así como fuentes de obtención, en población adulta brasileña. Se analizaron datos de adultos con una edad mayor o igual a 20 años, provenientes de la Encuesta Nacional sobre Acceso, Utilización y Promoción del Uso Racional de Medicamentos en Brasil (PNAUM), realizada entre septiembre de 2013 y febrero de 2014. La prevalencia de enfermedades respiratorias crónicas fue de un 3% (IC95%: 2,7-3,3). De estos, un 58,1% (IC95%: 51,8-64,0) tenían indicación de tratamiento farmacológico. De aquellos con indicación de tratamiento, un 77,1% (IC95%: 71,0-82,8) estaban utilizando, por lo menos, uno de los medicamentos indicados. El acceso total a la terapia fue de un 91,4% (IC95%: 79,9-96,6), siendo que más de la mitad de las personas con enfermedades respiratorias crónicas adquiría por lo menos uno de sus medicamentos en farmacias comerciales (57,3%). La clase de medicamentos más referida fue la asociación beta-2 agonista de larga duración y corticosteroides en forma inhalatoria, cuyo representante más frecuente fue la asociación budesonida/formoterol (20,3%; IC95%: 16,0-25,4). De acuerdo con nuestro estudio, la prevalencia de enfermedades respiratorias crónicas autoinformada fue inferior a trabajos previamente publicados para la población brasileña. Se verificó que casi la mitad de la población que refirió enfermedades respiratorias crónicas no tenía indicación de tratamiento farmacológico. Ya aquellos que tenían indicación, aproximadamente un cuarto, no utilizaba los medicamentos en el período del estudio y, para los que lo usaban, aunque el acceso fuese elevado, necesitaban pagar para adquirir sus tratamientos.

Indicação, acesso e utilização de medicamentos para doenças respiratórias crônicas no Brasil: resultados da Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos no Brasil (PNAUM), 2014 / Indication, access, and use of medicines for chronic respiratory diseases in Brazil: results from the National Survey on Access, Utilization, and Promotion of Rational Use of Medicines in Brazil (PNAUM), 2014 / Indicación, acceso y utilización de medicamentos para enfermedades respiratorias crónicas en Brasil: resultados de la Encuesta Nacional sobre Acceso, Utilización y Promoción del Uso Racional de Medicamentos en Brasil (PNAUM), 2014

O objetivo foi estimar a prevalência de doenças respiratórias crônicas autorreferidas, a indicação, o acesso e o uso de medicamentos, bem como fontes de obtenção, na população adulta brasileira. Foram analisados dados de adultos com idade maior ou igual a 20 anos, provenientes da Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos no Brasil (PNAUM), realizada entre setembro de 2013 e fevereiro de 2014. A prevalência de doenças respiratórias crônicas foi de 3% (IC95%: 2,7-3,3). Desses, 58,1% (IC95%: 51,8-64,0) tinham indicação de tratamento farmacológico. Daqueles com indicação de tratamento, 77,1% (IC95%: 71,0-82,8) estavam utilizando pelo menos um dos medicamentos indicados. O acesso total à terapia foi de 91,4% (IC95%: 79,9-96,6), sendo que mais da metade das pessoas com doenças respiratórias crônicas adquiria pelo menos um de seus medicamentos em farmácias comerciais (57,3%). A classe de medicamentos mais referida foi a associação beta-2 agonista de longa duração e corticosteroides sob a forma inalatória, cujo representante mais frequente foi a associação budesonida/formoterol (20,3%; IC95%: 16,0-25,4). De acordo com o nosso estudo, a prevalência de doenças respiratórias crônicas autorreferida foi inferior a trabalhos previamente publicados para a população brasileira. Verificou-se que quase metade da população que referiu doenças respiratórias crônicas não tinha indicação de tratamento farmacológico. Já aqueles com indicação, aproximadamente um quarto não utilizava os medicamentos no período do estudo e, para os que usavam, embora o acesso fosse elevado, precisavam pagar para adquirir seus tratamentos.

The study aimed to estimate the prevalence of self-reported chronic respiratory diseases and the indication, access to, and use of medicines, as well as their sources, in the Brazilian adult population. Data were analyzed on adults 20 years and older from the National Survey on Access, Utilization, and Promotion of Rational Use of Medicines in Brazil (PNAUM), conducted from September 2013 to February 2014. Prevalence of chronic respiratory diseases was 3% (95%CI: 2.7-3.3). Of these individuals, 58.1% (95%CI: 51.8-64.0) had an indication for pharmacological treatment. Of those with indication for treatment, 77.1% (95%CI: 71.0-82.8) were using at least one of the prescribed drugs. Total access to therapy was 91.4% (95%CI: 79.9-96.6), and more than half of individuals with chronic respiratory diseases purchased at least one of the drugs in retail pharmacies (57.3%). The most frequently reported drug class was the association of a corticosteroid plus a long-acting beta-2 agonist in inhalation form, the most common example of which was the association budesonide/formoterol (20.3%; 95%CI: 16.0-25.4). According to our study, prevalence of self-reported chronic respiratory diseases was lower than in previous studies published on the Brazilian population. Nearly half of the population reporting chronic respiratory diseases did not have an indication for pharmacological treatment. Among those with such indication, approximately one-fourth were not using medications during the study period, and for those who were on medication, although access was high, they had to pay for their medicines.

El objetivo fue estimar la prevalencia de enfermedades respiratorias crónicas autoinformadas, la indicación, el acceso y el uso de medicamentos, así como fuentes de obtención, en población adulta brasileña. Se analizaron datos de adultos con una edad mayor o igual a 20 años, provenientes de la Encuesta Nacional sobre Acceso, Utilización y Promoción del Uso Racional de Medicamentos en Brasil (PNAUM), realizada entre septiembre de 2013 y febrero de 2014. La prevalencia de enfermedades respiratorias crónicas fue de un 3% (IC95%: 2,7-3,3). De estos, un 58,1% (IC95%: 51,8-64,0) tenían indicación de tratamiento farmacológico. De aquellos con indicación de tratamiento, un 77,1% (IC95%: 71,0-82,8) estaban utilizando, por lo menos, uno de los medicamentos indicados. El acceso total a la terapia fue de un 91,4% (IC95%: 79,9-96,6), siendo que más de la mitad de las personas con enfermedades respiratorias crónicas adquiría por lo menos uno de sus medicamentos en farmacias comerciales (57,3%). La clase de medicamentos más referida fue la asociación beta-2 agonista de larga duración y corticosteroides en forma inhalatoria, cuyo representante más frecuente fue la asociación budesonida/formoterol (20,3%; IC95%: 16,0-25,4). De acuerdo con nuestro estudio, la prevalencia de enfermedades respiratorias crónicas autoinformada fue inferior a trabajos previamente publicados para la población brasileña. Se verificó que casi la mitad de la población que refirió enfermedades respiratorias crónicas no tenía indicación de tratamiento farmacológico. Ya aquellos que tenían indicación, aproximadamente un cuarto, no utilizaba los medicamentos en el período del estudio y, para los que lo usaban, aunque el acceso fuese elevado, necesitaban pagar para adquirir sus tratamientos.

Análise de custo-efetividade da abiraterona para câncer de próstata metastático resistente à castração em pacientes com uso prévio de quimioterapia / Cost-effectiveness analysis of abiraterone for metastatic, castrateresistant prostate cancer following previous chemotherapy

Objetivo: Avaliar a custo-utilidade e o impacto orçamentário (IO) da abiraterona para o tratamento de câncer de próstata resistente à castração, em pacientes previamente tratados com docetaxel. Métodos: Foi construído um modelo de Markov com ciclos mensais sob a perspectiva do Sistema Único de Saúde (SUS), em um horizonte temporal de cinco anos e taxa de desconto de 5%. A estimativa de efetividade foi oriunda do principal ensaio clínico dessa condição de saúde. Para dados de utilidade, aplicaram-se estimativas internacionais, enquanto para custos se utilizaram tabelas de remuneração do SUS. Para o IO, a população-alvo foi estimada com base em dados do Departamento de Informática do SUS (DATASUS). Resultados: A abiraterona ocasionou ganho de 1,045 ano de vida ajustado para qualidade (QALY) e 1,609 ano de vida ganho (AVG), enquanto para o placebo esses valores foram de 0,763 e 1,299, respectivamente. O custo total na estratégia abiraterona foi de R$ 83.295 e para o placebo, de R$ 2.895. A relação de custo-efetividade incremental (RCEI) foi de R$ 284.416 por QALY ganho. Em nenhuma das análises de sensibilidade os valores ficaram abaixo de R$ 100.000 por QALY. Mesmo quando variados simultaneamente seis parâmetros, todos no seu limite mais favorável à abiraterona, os resultados seguiram elevados, com RCEI de R$ 98.330 por QALY. O IO foi de R$ 270 milhões em cinco anos no cenário mais conservador (tempo médio de tratamento de 7,4 meses e 10% de novos casos/ano). Conclusão: A abiraterona se mostrou pouco custo-efetiva nesta situação clínica, com RCEI superior a nove vezes o PIB per capita por QALY, sendo os resultados robustos em análise de sensibilidade.

Objective: To evaluate the cost-utility and the budget impact (BI) of abiraterone in patients with castration-resistant prostate cancer previously treated with docetaxel. Methods: A Markov model was constructed, with monthly cycles, under the perspective of the Brazilian Public Healthcare System (SUS), in a 5-year time horizon, and with a 5% discount rate. The effectiveness estimate was obtained from the pivotal clinical trial for abiraterone in this health condition. For utility data, international estimates were applied; while for costs, SUS reimbursement information were used. In the BI analysis, the target population was estimated with claims data from DATASUS. Results: Abiraterone resulted in a gain of 1.045 quality-adjusted life years (QALY) and 1.609 life years gained (LYG), while for placebo these values were 0.763 and 1.299, respectively. The total cost for the abiraterone strategy was BRL 83,295, and for placebo, BRL 2,895. The incremental cost-effectiveness ratio (ICER) was BRL 284,416 per QALY gained. None of the estimates from the sensitivity analysis was below BRL 100,000 per QALY. Even when six parameters were variated simultaneously in the range more favorable to abiraterone, the results were still elevated, with an ICER of BRL 98,330 per QALY. The BI was BRL 270 million in 5 years in the most conservative scenario (average time of the treatment of 7.4 months and 10% of the new cases/year). Conclusion: Abiraterone shows unfavorable cost-effective results for this clinical condition in Brazil, with an ICER above 9 times the per capita per QALY. Results were robust in sensitivity analysis.

Glutamate promotes cell growth by EGFR signaling on U-87MG human glioblastoma cell line.

Accumulating evidences suggest that glutamate plays a key role in the proliferation and invasion of malignant glioblastoma (GBM) tumors. It has been shown that GBM cells release and exploit glutamate for proliferation and invasion through AMPA glutamate receptors. Additionally, amplification of the epidermal growth factor receptor (EGFR) gene occurs in 40-50% of GBM. Since, PI3K/Akt is considered one of the main intracellular pathways involved in EGFR activation, AKT functions could trigger EGFR signaling. Thus, we investigated whether EGFR-phospho-Akt pathway is involved on the glutamate inducing U-87MG human GBM cell line proliferation. For these purpose, we treated the U-87MG cell line with 5 to 200 mM of glutamate and assessed the number of viable cells by trypan blue dye exclusion test. An increase in cell number (50%) was found at 5 mM glutamate, while the addition of DNQX (500 microM), an antagonist of AMPA receptor, inhibited the effect of glutamate on the U87-MG cells proliferation. Also, at 5 mM glutamate we observed an increase on the EGFR and phospho-Akt contents evaluated by immunohistochemistry. Moreover, U-87MG cells treated with glutamate exhibited an increase about 2 times in the EGFR mRNA expression. While, in the presence of the anti-EGFR gefitinib (50 muM) or the PI3K inhibitor wortmannin (5 muM), the U-87MG proliferation was restored to control levels. Together, our data suggest that glutamate signaling mediated by AMPA receptor induces U-87MG human GBM cell line proliferation via EGFR-phospho-Akt pathway.